The present invention, in some embodiments thereof, relates to chemistry and, more particularly, but not exclusively, to a novel family of polycyclic (e.g., macrocyclic) compounds which can serve as host molecules and utilized in a myriad of applications.
Polycyclic compounds are defined as linear or cyclic compounds that exhibit a plurality of cyclic moieties linked to one another either directly or indirectly. Polycyclic compounds can be assembled into various cyclic structures, often referred to in the art as macrocyclic compounds. Some macrocyclic compounds are known to act as host molecules to other, guest species.
Macrocyclic host molecules are employed in a large variety of applications and technologies in the fields of chemistry, biology, food, electronics, printing, etc. Macrocyclic host molecules exhibit specific host-guest reversible binding, governed by their chemical nature.
One of the four main known families of macrocyclic host molecules are calixarenes. Calixarenes are basically comprised of phenols that are linked to one another by a short alkylene bridge. Each calixarene contains a repeating phenolic unit formed into a macrocycle via alkylene, typically methylene, bridges. Calixarenes are the product of condensation of phenols and aldehydes. The phenolic unit can be derived from phenol, resorcinol or pyrogallol, and the aldehyde used can be simply a formaldehyde or a larger aldehyde, depending on the nature of the phenolic unit and the desired properties of the formed calixarene. In heterocalixarenes, the phenolic units are replaced by heterocycles, for instance by furans in calix[n]furanes and by pyridines in calix[n]pyridines.
Calixarenes are sparingly soluble and are high temperature melting crystalline solids.
Calixarene nomenclature incorporates the number of repeating aromatic units in the ring. A calix[4]arene has 4 phenols in the ring and a calix[6]arene has 6. A substituent in the meso position (of the carbon atom in a methylene bridging unit) is added to the name with a prefix C- as in, for example, C-methylcalix[6]arene.
Calixarenes are cup-shaped molecules that can form inclusion complexes with a wide range of guest species. The Calixarene “cups” have a vaselike structure defined by an upper rim, lower rim, and central annulus. In calix[4]arenes the internal volume is around 10 cubic nanometers. The polar and non-polar features of the cavities enable calixarenes to interact with a wide range of guest species, depending on the binding groups substituted at each rim and the number of repeating units in the macrocycle.
An exemplary common calixarene, p-tert-butylcalix[4]arene has the following chemical structure:

Calixarenes have been used in a wide variety of fields, such as non linear optics, in the field of cation complexation, as sensor devices, in nuclear waste treatment, and as a catalyst in synthetic reactions and liquid crystals. Being efficient sodium ionophores, and capable of exhibiting great selectivity towards other cations, calixarenes are commonly used in chemical sensors, e.g., in commercial applications as sodium selective electrodes for the measurement of sodium levels in blood. Calixarenes also form complexes with cadmium, lead, lanthanides and actinides.
Calixarenes are also applied in enzyme mimetics, ion sensitive electrodes or sensors, selective membranes, non-linear optics and in HPLC stationary phase. In addition, in nanotechnology, calixarenes are used as negative resist for high-resolution electron beam lithography.
Calixarenes are able to accelerate reactions taking place inside the cavity by a combination of local concentration effect and polar stabilization of the transition state.
Currently known sulfur-containing calixarenes include thiacalixarenes, in which there is a thioether bridge between the aromatic units, and, more rarely, thiolcalixarenes (also called mercaptocalixarenes), in which the hydroxyl groups of the phenols are converted to thiols. Exemplary such sulfur-containing calixarenes are described, for example, in H. Kumagai et al., Tetrahedron Lett. 1997, 38, pp 3971-397 and in C. G. Gibbs et al., J. Org. Chem., 1995, 60 (26), pp 8394-8402, as well as in U.S. Pat. No. 6,268,320.
Macrocycles composed of units derived from urea, which have aromatic moieties fused thereto, have been synthesized in the past in low yields. The mechanisms by which these compounds are synthesized (alkaline conditions) preclude use of this synthesis to produce a thiaureatic-containing macrocycle (due to the sulfur's nucleophilicity). Examples of such compounds are described in P. R. Dave et al., J. Org. Chem., 1995, 60 (21), pp 6946-6952 and in E. Weber et al., J. Chem. Soc., Perkin Trans. 2, 1996, pp. 2359-2366.